Histone acetyltransferases (HATs) are involved in the epigenetic positive control of gene expression in eukaryotes. CREB-binding proteins (CBP)/p300, a subfamily of highly conserved HATs, have been shown to function as acetylases on both histones and non-histone proteins. In the model plant Arabidopsis thaliana among the five CBP/p300 HATs, HAC1, HAC5 and HAC12 have been shown to be involved in the ethylene signaling pathway. In addition, HAC1 and HAC5 interact and cooperate with the Mediator complex, as in humans. Therefore, it is potentially difficult to discriminate the effect on plant development of the enzymatic activity with respect to their Mediator-related function. Taking advantage of the homology of the human HAC catalytic domain with that of the Arabidopsis, we set-up a phenotypic assay based on the hypocotyl length of Arabidopsis dark-grown seedlings to evaluate the effects of a compound previously described as human p300/CBP inhibitor, and to screen previously described cinnamoyl derivatives as well as newly synthesized analogues. We selected the most effective compounds, and we demonstrated their efficacy at phenotypic and molecular level. The in vitro inhibition of the enzymatic activity proved the specificity of the inhibitor on the catalytic domain of HAC1, thus substantiating this strategy as a useful tool in plant epigenetic studies.

New Inhibitors of the human p300/CBP acetyltransferase are selectively active against the Arabidopsis HAC proteins / Longo, Chiara; Lepri, Andrea; Paciolla, Andrea; Messore, Antonella; DE VITA, Daniela; BONACCORSI DI PATTI, Maria Carmela; Amadei, Matteo; Madia, VALENTINA NOEMI; Ialongo, Davide; DI SANTO, Roberto; Costi, Roberta; Vittorioso, Paola. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 23:18(2022), pp. 1-18. [10.3390/ijms231810446]

New Inhibitors of the human p300/CBP acetyltransferase are selectively active against the Arabidopsis HAC proteins

Chiara Longo
Co-primo
Investigation
;
Andrea Lepri
Co-primo
Investigation
;
Antonella Messore;Daniela De Vita;Maria Carmela Bonaccorsi di Patti;Matteo Amadei;Valentina Noemi Madia;DAVIDE IALONGO;Roberto Di Santo;Roberta Costi;Paola Vittorioso
Ultimo
Supervision
2022

Abstract

Histone acetyltransferases (HATs) are involved in the epigenetic positive control of gene expression in eukaryotes. CREB-binding proteins (CBP)/p300, a subfamily of highly conserved HATs, have been shown to function as acetylases on both histones and non-histone proteins. In the model plant Arabidopsis thaliana among the five CBP/p300 HATs, HAC1, HAC5 and HAC12 have been shown to be involved in the ethylene signaling pathway. In addition, HAC1 and HAC5 interact and cooperate with the Mediator complex, as in humans. Therefore, it is potentially difficult to discriminate the effect on plant development of the enzymatic activity with respect to their Mediator-related function. Taking advantage of the homology of the human HAC catalytic domain with that of the Arabidopsis, we set-up a phenotypic assay based on the hypocotyl length of Arabidopsis dark-grown seedlings to evaluate the effects of a compound previously described as human p300/CBP inhibitor, and to screen previously described cinnamoyl derivatives as well as newly synthesized analogues. We selected the most effective compounds, and we demonstrated their efficacy at phenotypic and molecular level. The in vitro inhibition of the enzymatic activity proved the specificity of the inhibitor on the catalytic domain of HAC1, thus substantiating this strategy as a useful tool in plant epigenetic studies.
2022
Arabidopsis thaliana; HAC proteins; p300/CBP inhibitors
01 Pubblicazione su rivista::01a Articolo in rivista
New Inhibitors of the human p300/CBP acetyltransferase are selectively active against the Arabidopsis HAC proteins / Longo, Chiara; Lepri, Andrea; Paciolla, Andrea; Messore, Antonella; DE VITA, Daniela; BONACCORSI DI PATTI, Maria Carmela; Amadei, Matteo; Madia, VALENTINA NOEMI; Ialongo, Davide; DI SANTO, Roberto; Costi, Roberta; Vittorioso, Paola. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 23:18(2022), pp. 1-18. [10.3390/ijms231810446]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1654141
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